A Self-Immolative Spacer That Enables Tunable Controlled Release of Phenols under Neutral Conditions

A current challenge in the area of responsive materials
is the
design of reagents and polymers that provide controlled release of
phenols in environments that are less polar than water. In these contexts,
a molecular strategy that enables release of nearly any phenol with
predictable and tunable rates and without complication from background
hydrolysis would substantially increase the precision with which materials
can be designed to respond to a particular signal. This Article addresses
this problem at the fundamental level by describing the design, synthesis,
and physical-organic characterization of two small molecule self-immolative
spacers that are capable of releasing phenols in organic and mixed
organic–aqueous solutions. The rate of release from these small
molecule model systems is predictable and tunable, such that nearly
any type of phenol, regardless of pKa value,
can be released in neutral solutions without complications from nonspecific
background release due to hydrolysis. Furthermore, the release properties
of the spacers can be predicted from bond length and conformation
data (obtained from crystal structures). On the basis of these results,
it should now be possible to incorporate these design elements into
materials to enable precise response properties in environments that
are not 100% aqueous.